The activation of mast cells and basophils by immunoglobulin cell surface receptors results in the release of an array of mediators. The goal of this project is to understand the mechanism of signal transduction from the immune receptors. The receptors on these cells are a model for studies of immunoglobulin receptors present on many immune cells such as B, T cells and monocytes. This project investigates the receptors and the molecular mechanisms involved in signal transduction in these cells. The model used for most of these studies is the rat basophilic leukemia RBL- 2H3 cell line. Goals are to characterize and identify the proteins which are activated in the signal cascade from the cell surface receptors that result in activation of cells to secrete granules. Emphasis has been on understanding the protein tyrosine phosphorylations that occur during cell activation, especially the activation of the protein kinase Syk. Studies identify the protein tyrosine kinases that are involved in these reactions together with their substrates. We are using immunological, biochemical, molecular and cell biological techniques.